(A) Fold-enrichment of CLEC7A, c.714T>G; p.Y238* variant in patients with DCM compared with the gnomAD. Normalized to frequency of homozygous WT or variant carriers in gnomAD. P = 0.0303, Fisher’s exact test. (B) Parallel signaling pathways after β-glucan recognition by DECTIN-1 leading to activation of NF-κB and NFAT transcription factors and production of TNF-α. The figure was created using BioRender. (C) Confocal microscopy of lung from C. posadasii–infected C57BL/6 mouse showing DECTIN-1 (red) localized near endospores (blue) (left), LAMP-1 (green) localization near endospores (middle), and colocalization of DECTIN-1 and LAMP-1 (tan) around endospores (right). (D) Frequency of patients of European ancestry with DCM with PLCG2, c.802C>T; p.R268W genotype normalized to the non–Finnish European population in gnomAD. P = 0.0077 Fisher’s exact test. (E) Particulate β-glucan–induced TNF production by PBMCs from patients (n = 16) or healthy control (HC) participants (n = 12). DECTIN-1 variants (n = 4) include homozygous p.Y238* (filled) and heterozygous p.Y238* (open). Patients withPLCG2 variants (n = 6) include p.R268W heterozygotes (yellow symbols), p.M28L heterozygotes (green symbol), and p.R268W and p.K775R compound heterozygotes (open yellow symbol). Patients in the “other” category (n = 6) lack identified causal variants. P values were calculated using Brown-Forsythe and Welch ANOVA with Dunnett’s T3 multiple comparisons test. (F) Frequency of Y238* among East Asian patients from DCM validation cohort compared with the 1000G and gnomAD.